Density and viscosity studies of aspirin in aqueous

Trade Science Inc. Editorial Office : 126 Prasheel Park, SanjayRaj Farm House, Nr. Saurashtra University, Rajkot 360 005, Gujarat - INDIA.

MANUSCRIPT ACCEPTANCE REPORT 25th November, 2010 Ph68482201 Date : ___________________________________ Manuscript No.: __________________________ Physical Chemistry : An Indian Journal Journal Name : _____________________________________________________________________ Mazahar Farooqui, Muktar Shaikh Author(s) : ________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ Density and viscosity studies of aspirin in aqueous ethanol system at 301.5k MS Title:_________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ Published by : Trade Science Inc. Copyright @ Trade Science Inc.

Mazahar Farooqui Dear Prof.Dr.________________________________________________________________________ EDITORIAL DECISION Your manuscript is accepted ìn its present form by our editorial board members.

Thank you very much for submission of your valuable research work.

Production Department

Trade Science Inc

Trade Science Inc. Editorial Office : 126 Prasheel Park, SanjayRaj Farm House, Nr. Saurashtra University, Rajkot 360 005, Gujarat - INDIA.

COPYRIGHT TRANSFER AGREEMENT th

Ph68482201 25 November, 2010 Date : ___________________________________ Manuscript No.: __________________________ Physical Chemistry : An Indian Journal Journal Name : _____________________________________________________________________ Mazahar Farooqui, Muktar Shaikh Author(s) : ________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ Density and viscosity studies of aspirin in aqueous ethanol system at 301.5k MS Title:_________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ Published by : Trade Science Inc. Copyright @ Trade Science Inc. Thank you for submitting your work for publication. In order to expedite the editing and publishing process and enable Trade Science Inc. to disseminate your work to the fullest extent, we need to have this Copyright Transfer Agreement signed and returned to us as soon as possible. COPYRIGHT TRANSFER 1.

The contributor assigns to Trade Science Inc., during the full term of copyright and any extensions or renewals of that term, all copyright in and to the contribution, including but not limited to the right to publish, republish, transmit, sell, distribute and otherwise use the contribution and the material contained therein in electronic and print editions of the Journal and in derivative works, in all languages and in all media of expression now known or later developed, and to license or permit others to do so.

2.

Reproduction, posting, transmission or other distribution or use of the contribution or any material contained therein, in any medium as permitted hereunder, requires a citation to the Journal and an approximate credit to Trade Science Inc. as Publisher, suitable in form and content as follows:

Density and viscosity studies of aspirin in aqueous ethanol system at 301.5k MS Title:_________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ Farooqui, Muktar Shaikh Author(s) : Mazahar ________________________________________________________________________ __________________________________________________________________________________ __________________________________________________________________________________ Physical Chemistry : An Indian Journal Journal Name : _____________________________________________________________________

RETAINED RIGHTS Notwithstanding the above, the contributor retains all proprietary rights other than copyright, such as patent rights, in any process, procedure or article of manufacture described in the contribution, and the right to make oral presentations of material from the contribution.

OTHER RIGHTS OF CONTRIBUTOR 1.The right to share with colleagues print or electronic “preprints” of the unpublished contribution, in form and content as accepted by Trade Science Inc. for publication in the Journal. Such preprints may be posted as electronic files on the contributor’s own website for personal or professional use, or on the contributor’s internal university or corporate networks/internet, or secure external website at the contributor’s institution, but not for commercial sale or for any systematic external distribution by a third party. Prior to publication, the contributor must include the following notice on the preprint: “This is preprint of an article accepted for publication in (Journal Title)  Copyright (year) (Copyright owner as specified in the Journal)”. 2.The right, without change, to photocopy or to transmit online or to download, print out and distribute to a colleague a copy of the published contribution in whole or in part, for the colleague’s personal or professional use, for the advancement of scholarly or scientific research or study. 3.The right to republish, without charge, in print format, all or part of the material from the published contribution in a book written or edited by the Contributor. 4.The right to use selected figures and tables, and selected text (up to 200 words, exclusive of the abstract) from the contribution, for the Contributor’s own teaching purposes, or for incorporation within another work by the Contributor i.e. made part of an edited work published (in print or electronic format) by a third party, or for presentation in electronic format or an external website of the Contributor.

COPYRIGHT NOTICE The Contributor and the Company agree that any and all copies of the contribution or any part thereof distributed or posted by them in print or electronic format as permitted herein will include the notice of copyright as stipulated in the Journal and a full citation to the Journal as published by Trade Science Inc.

CONTRIBUTOR’S REPRESENTATIONS The contributor represents that the contribution is the contributor’s original work. If the contribution was prepared jointly, the contributor agrees to inform the co-contributors of the terms of this Agreement and to obtain their signature to this Copyright Transfer Agreement or their written permission to sign on their behalf. The contribution is submitted only to this Journal and has not been published before, except for “preprints” as permitted above. The contributor also warrants that the contribution contains no libelous or unlawful statements, doesn’t infringe upon the rights (including without limitation the copyright, patent or trademark rights) or the privacy of others, or contain material or instructions that might cause harm or injury.

Contributor(s) Name(s)

Contributor(s) Signature(s)

___________________________________________________________________________________ ___________________________________________________________________________________ ___________________________________________________________________________________ ___________________________________________________________________________________ ___________________________________________________________________________________ ___________________________________________________________________________________ Send Signed COPYRIGHT TRANSFER AGREEMENT by Post

Tips for checking Galley Proof

1. 2.

3. 4.

5. 6. 7.

8.

Print Guidelines for Publication available at http://www.tsijournals.com Carefully check, (i) Title, (ii) Authors and Addresses, (iii) Corresponding Author’s E-mail Address, (iv) Abstract, (v) Keywords, (vi) Introduction, (vii) Experimental, (viii) Results and Discussion, (ix) Conclusions , (x) Acknowledgment, (xi) References and Footnotes. Make sure all symbols, subscripts, superscripts, equations, reaction schemes, chemical structures, legend of figures, captions of tables are correct. It is corresponding author’s responsibility to check sent galley proof. If once correction(s) will be receive , we are not taking any responsibility regarding remained/not corrected information. 2nd galley proof will not be sent in any case. No claim will be considered after ms is published. Corrected galley proof must be returned within 3 days after receiving via email at [email protected] with subject line galley proof and manuscript number. If we aren’t receiving galley proof within 4 days we will publish manuscript in as appeared as in galley proof.

Galley Proof Depatment Trade Science Inc.

Manuscript Information of : Ph68482201 Publish in Journal : Physical Chemistry : An Indian Journal Manuscript Title : "Density & Viscosity studies of cyproheptadine-HCl in mixed binary solvent in presence of additives" Submission Date : 9/22/2010 Corresponding Author : Mazahar N Farooqui MS Type : Full Paper

Full Paper Density and viscosity studies of aspirin in aqueous ethanol system at 301.5k Mazahar Farooqui1* Muktar Shaikh2 2

1 Post Graduate and Research Centre, Maulana Azad College, Aurangabad, (INDIA) Department of Chemistry, Shri Anand College, Pathardi, Dist-Ahmednagar, (INDIA) E-mail : [email protected] Received: 22nd September, 2010 ; Accepted: 2nd October, 2010

ABSTRACT

KEYWORDS Aspirin; Partial molar volume; Gibbs free energy of viscous flow; Excess viscosity.

Density and Viscosity of drug Aspirin (APN) in various aqueous mixtures of ethanol have been determined. These results are further extended for solutes like electrolyte NaCl and non-electrolyte sucrose in the presence of this drug. The density and viscosity data have been analyzed for the evaluation of partial molar volume, molar excess volume, Gibbs free energy of viscous flow, excess viscosity and A and B viscosity coefficients using Jones-Dole equation. It can be inferred from these studies that this drug acts as a structure-making compound due to hydrophobic hydration of drug molecules. B-coefficients values are found to be positive thereby showing drug solvent interactions. Furthermore these results are correlated to understand the solution behavior of drug.  2011 Trade Science Inc. - INDIA

INTRODUCTION Solute-solvent interactions play an important role in a variety of phenomena. In bio-physical chemistry, drug interaction is a subject of intensive studies, involving complex molecular mechanisms. Despite years of investigations, many important drug actions and their mechanisms are not fully understood. Solute-solvent interaction studies have been a subject of active interest among physical chemists[1,2] and mostly the inferences regarding these interactions are drawn from molar volume data[3] & viscosity data[4] together. Most of the drugs are organic molecules with both hydrophobic and hydrophilic groups. These molecules often contain certain groups, which are responsible for their acidic, basic or amphoteric properties. Pharma-

cological properties[5,6] of drugs are highly dependent on the solution behavior. The thermodynamic properties are the convenient parameter for interpreting solute-solvent interactions in the solution phase, which ultimately explain the excess properties using different interaction parameters. In the present communication an attempt has been made to study density and viscosity measurements of Aspirin in aqueous ethanol to investigate various types of interactions. HO

O O

O

Structure of aspirin

6

Density and viscosity studies of aspirin in aqueous ethanol system at 301.5k

Full Paper TABLE 1 : Density  (g cm–3) of APN in binary system at 301.5K v/v % Et-OH 20

TABLE 2: Viscosity  (m Pa. s) ofAPN in binary system at 301.5K

0.02 M

0.04 M

0.06 M

0.08M

0.10 M

0.9968

1.0005

1.0041

1.0075

1.0114

v/v % Et-OH 20

40

0.9723

0.9762

0.9798

0.9833

0.9867

60

0.9461

0.9496

0.9532

0.9568

0.9607

80

0.9069

0.9104

0.9142

0.9178

100

0.8148

0.8184

0.8217

0.8256

0.02 M

0.04 M

0.06 M

0.08M

0.10 M

1.7063

1.7135

1.7251

1.7286

1.7498

40

2.3374

2.3513

2.3748

2.3873

1.7395

60

2.4182

2.4376

2.4543

2.4654

2.3979

0.9214

80

1.9863

1.9906

2.0867

2.1880

2.4818

0.8293

100

1.3691

1.3745

1.3911

1.4131

2.3048

ñ of APN +0.01 M NaCl v/v % Et-OH 20

ç of APN +0.01 M NaCl

0.02 M

0.04 M

0.06 M

0.08M

0.10 M

0.9974

1.0011

1.0047

1.0082

1.0119

v/v % Et-OH 20

40

0.9730

0.9765

0.9803

0.9838

0.9874

60

0.9468

0.9502

0.9538

0.9576

0.9612

80

0.9073

0.9111

0.9146

0.9181

100

0.8153

0.8188

0.8226

0.8261

0.02 M

0.04 M

0.06 M

0.08M

0.10 M

1.7158

1.7233

1.7389

1.7428

1.7471

40

2.3458

2.3692

2.3885

2.4064

2.4274

60

2.4466

2.3827

2.4717

2.4896

2.5182

0.9219

80

1.9906

1.9627

2.1464

2.2848

2.3317

0.8296

100

1.3717

1.3986

1.4023

1.4447

1.4544

ñ of APN +0.01 M Sucrose v/v % Et-OH 20

ç of APN +0.01 M Sucrose

0.02 M

0.04 M

0.06 M

0.08M

0.10 M

0.9996

1.0038

1.0076

1.0112

1.0146

v/v % Et-OH 20

40

0.9754

0.9796

0.9832

0.9868

0.9904

60

0.9491

0.9532

0.9568

0.9604

0.9638

80

0.9098

0.9139

0.9176

0.9212

100

0.8173

0.8217

0.8254

0.8288

0.02 M

0.04 M

0.06 M

0.08M

0.10 M

1.7318

1.7582

1.7613

1.7844

1.8093

40

2.3815

2.3908

2.4018

2.4650

2.5064

60

2.5614

2.5864

2.5984

2.6171

2.6390

0.9248

80

2.1196

2.1321

2.3589

2.4502

2.4708

0.8324

100

1.4009

1.4255

1.4367

1.5584

1.6478

EXPERIMENTAL Materials The binary solvent selected for the study was ethanol + water. Commercial ethyl alcohol is refluxed with CaO for six to eight hours and distilled[7]. Double distilled water is used for preparation of solution mixture. The distillation of water was carried out using a pinch of KMnO4 & KOH in glass quick fit apparatus. The density and viscosity of water and ethanol are measured at 298.15 K and 303.15 K and compared with literature values. Apparatus and procedure Densities of liquids and various solutions were measured at 301.5K by using specific gravity bottle of 10 cm3 capacity. A single pan electronic balance [Sansui; model KD-UBED of capacity 120 gm and with a precision of 0.0001 gm] was used for weighing purpose. The weighing was repeated thrice to ensure the accuracy in weights with a little interval of time. The reproducibility of the result was close to hundred percent.

Viscosity measurements were carried out using Ostwald’s viscometer with precision ± 0.1 %. The viscometer was clamped vertically in a thermostatically controlled water-bath, whose temperature was maintained constant at 301.5K (± 0.02°C). A fixed volume (10ml) of the solution was delivered into the viscometer. The viscometer was kept for 30 minutes in the thermostatically controlled water-bath to achieve constant temperature. The experiments of measurements of flow time of the solution between the two points on the viscometer were performed at least three times for each solution and the average results were noted. RESULTS AND DISCUSSION Aspirin is chemically 2-acetoxybenzoic acid. It is white crystals, commonly tabular or needle-like, or a white, crystalline powder; odorless or a faint odor; stable in dry air. The densities and viscosities of ethanol- water binary mix from 20 % to 100 % range are measured

Mazahar Farooqui and Muktar Shaikh

7

Full Paper TABLE 3a : Ôv in cm3 mol-1 and VE in cm3 mol-1 of APN in binary mixture at 301.5 K V/V % Et- OH

0.02 M (APN)

0.04 M (APN)

VE

Ôv

Ôv

0.06 M (APN)

VE

VE

Ôv

TABLE 3b : Ôv in cm3 mol-1 and VE in cm3 mol-1 of (APN) +0.01 M NaCl in binary mixture at 301.5 K V/V % Et- OH

0.02 M (APN)

0.04 M (APN)

0.06 M (APN)

Ôv

Ôv

Ôv

Ôv

Ôv

Ôv

20

180.0856 -0.9168 179.2601 -0.9910 177.5838 -1.0627

20

58.5571

58.5571

58.3408

58.3408

58.1319

58.1319

40

184.6256 -1.5869 183.7961 -1.6804 181.9038 -1.7661

40

60.0185

60.0185

59.8280

59.8280

59.5840

59.5840

60

189.6993 -2.5552 188.9828 -2.6598 186.9829 -2.7665

60

61.6781

61.6781

61.4640

61.4640

61.2322

61.2322

80

197.8443 -3.6481 197.0650 -3.7899 194.8266 -3.9426

80

64.3825

64.3825

64.0930

64.0930

63.8688

63.8688

220.0783 -2.3229 218.9802 -2.5712 216.5845 -2.7969

100

71.6352

71.6352

71.3379

71.3379

70.9653

70.9653

100

0.08 M (APN)

0.10 M (APN)

V/V % Et- OH

Ôv

V

Ôv

V

V/V % Et- OH

20

176.7778

-1.1299

176.0159

-1.2064

40

181.1329

-1.8488

180.3863

-1.9286

60

186.1099

-2.8725

185.1875

E

E

0.08 M (APN)

0.10 M (APN) Ôv

VE

57.7242

-1.1457

57.7242

59.1438

-1.8621

59.1438

-2.8985

60.7674

-2.8985

60.7674

-4.0990

63.3564

-4.0990

63.3564

-3.0973

70.4181

-3.0973

70.4181

Ôv

V

57.9244

-1.1457

59.3721

-1.8621

-2.9864

60.9766

80

193.7931

-4.0861

192.9396

-4.2285

63.6324

100

215.2039

-3.0614

214.0213

-3.3100

70.6992

E

TABLE 3c : Ôv in cm3 mol-1 and VE in cm3 mol-1 of (APN) +0.01 M sucrose in binary mixture at 301.5 K V/V % Et- OH

Figure 1 : Variation of E with% ethanol

0.02 M (APN)

0.04 M (APN)

E

E

V

Ôv

Ôv

V

0.06 M (APN) VE

Ôv

20

341.1785 -0.9751 339.5852 -1.0616 338.2414 -1.1396

40

349.5110 -1.6638 347.9104 -1.7667 346.6409 -1.8543

60

359.2024 -2.6474 357.4364 -2.7725 356.0966 -2.8813

80

374.7086 -3.7683 372.7872 -3.9369 371.3304 -4.0872

100

417.1710 -2.4984 414.5388 -2.8043 412.4872 -3.0601 0.08 M (APN)

0.08 M (APN)

V/V % Et- OH

Ôv

V

20

336.9745

40

E

Ôv

VE

-1.2133

336.9745

-1.2133

345.3455

-1.9416

345.3455

-1.9416

60

354.7668

-2.9893

354.7668

-2.9893

80

369.8846

-4.2325

369.8846

-4.2325

100

411.0516

-3.2904

411.0516

-3.2904

(TABLE 1 and 2) and used for determination of partial molar volume. The partial molar volume v was obtained from density results using eq. 1 v 

Figure 2 : Variation of G*E with % ethanol

1000  d o d  M   C  d  d

(1)

where do is the density of pure solvent & d is the density of solution, c is molar concentration, M is molar mass of drug. Aspirin consist of bulkier carboxylic and acetate group. It is observed that the v values decreases with concentration of APN and increases with increase in percentage of alcohol (TABLE 3).

8

Density and viscosity studies of aspirin in aqueous ethanol system at 301.5k

Full Paper TABLE 4 : Excess viscosities (çE) : - (mPas) V/V % Et- OH

0.02 M

0.04 M

0.06 M

0.08 M

TABLE 5 : Gibbs free energy of viscous flow ÄG*E( kJ mole-1) 0.10 M

V/V% Et-OH

0.02 M

Ethanol-water + (APN)

0.04 M

0.06 M

0.08 M

0.10 M

58.4344

62.7108

Ethanol-water + APN

20

0.9890

0.9962

1.0078

1.0113

1.0222

20

46.3301

50.3194

54.5241

40

1.5954

1.6093

1.6328

1.6453

1.6559

40

70.8388

77.2882

84.1162

90.6377

97.1606

60

1.6398

1.6592

1.6759

1.6870

1.7034

60

82.9775

90.0794

97.1325

104.0027

111.1286

80

1.1489

1.1532

1.2493

1.3506

1.4674

80

80.3369

85.7136

96.2390

107.4665

119.9832

100

0.4195

0.4249

0.4415

0.4635

0.4881

100

54.8506

58.0204

62.5937

67.9387

73.8263

Ethanol-water + (APN) + 0.01 M Sucrose

Ethanol-water + APN + 0.01 M Sucrose

20

1.0145

1.0409

1.0440

1.0671

1.0920

20

50.8367

55.7521

59.7715

64.8481

70.1958

40

1.6395

1.6488

1.6598

1.7230

1.7644

40

77.9417

84.3584

90.8573

99.5563

107.6675

60

1.7830

1.8080

1.8200

1.8387

1.8606

60

94.0835 101.8277 109.1786 116.8446

124.7641

80

1.2822

1.2947

1.5215

1.6128

1.6334

80

92.3301

98.6808

117.0594 128.4104

135.8726

100

0.4513

0.4759

0.4871

0.6088

0.6982

100

60.9882

66.6451

70.8725

103.9187

Ethanol-water + (APN) + 0.01 M NaCl

89.1992

Ethanol-water + APN + 0.01 M NaCl

20

0.9985

1.0060

1.0216

1.0255

1.0298

20

47.2662

51.3144

55.7482

59.7389

63.7331

40

1.6038

1.6272

1.6465

1.6644

1.6854

40

72.0542

78.8728

85.5990

92.3827

99.4007

60

1.6682

1.6043

1.6933

1.7112

1.7398

60

84.9585

89.0395

98.8725

106.0773

113.8874

80

1.1532

1.1253

1.3090

1.4474

1.4943

80

81.4046

84.9315

100.5868 114.1301

122.6052

100

0.4221

0.4490

0.4527

0.4951

0.5048

100

55.5588

61.3000

64.3946

76.5569

The density data was also used to evaluate excess molar volumes (TABLE 3) calculated by using the relation (eq. 2).  x M  x 2M 2 V E   1 1  

 x1M1 x 2 M 2    l 2 

(2)

where,  is the density of mixture, M1, X1, V1 and M2, X2 & V2 are the molecular weight, mole fraction and molar volumes of ethanol & water respectively. The excess molar volumes calculated for APN in absence and in presence of additives are negative. We observed that VE changes parabolically in negative direction with % of ethanol. Over all range of concentration it was observed that VE values are less in absence of additives and slightly high when NaCl is used. But in presence of sucrose these values are higher in negative direction. This indicates more solubility of it in the mixture. The parabolic shape of VE against % ethanol is characterized by well defined minima which indicate the presence of complex form between mixing components of solution. The excess volume of mixture containing APN with and without additives is shown in TABLE 3. These values are positive and changes in parabolic way with the % of ethanol. The higher values of excess viscosities of

72.4694

non-electrolyte in binary system may be due to the presence of larger and bulkier groups. Viscosity is found to maximum at around 50% (V/ V) in aqueous mixtures of alcohol. It seems that some kind of structural organization of water surrounding the hydrocarbon chain of alcohol is the most likely explanation of the observed dependence of viscosity on solvent composition. The measured values of viscosities of liquid mixtures and those of pure components were used to calculate the excess viscosity E (TABLE 4) in the liquid mixtures using the formula (eq. 3), E = mix –(x11 - x22)

(3)

where, mix, 1 & 2 are the viscosities of liquid mixtures, component (1) & (2) respectively and x1 & x2 are the mole fractions of component (1) & (2) respectively. The hydrocarbon residue of APN in alcohol results in a considerable amount of hydrophobic hydration. However the further decrease of excess viscosity with increase in percentage alcohol may result because these hydrophobic groups exerts there effect predominantly with increase in alcohol percent (Figure 1). It appears that above 60 % v/v alcohol concentration a loss of

Mazahar Farooqui and Muktar Shaikh

9

Full Paper TABLE 6 : A and B coefficient values V/V% Et-OH

(APN)

(APN) +0.01 Sucrose A B

(APN) +0.01 NaCl A B

A

B

20

2.1994

0.0641

2.6456

0.0976

2.1639

0.0698

40

2.1894

0.0695

2.7082

0.1090

2.1985

0.0693

60

2.4844

0.0839

3.4030

0.1284

2.6351

0.0948

80

2.9165

0.0958

4.4502

0.1581

3.3395

0.1121

100

3.3706

0.1106

5.0488

0.1785

3.4954

0.1217

hydrophobic hydration takes place which leads to decrease in excess viscosity[8]. On the basis of the theory of absolute reaction rates, the excess Gibb’s free energy of activation for viscous flow, GE[9,10] were calculated (TABLE 5)for all the system under study using the equation: *E

G = RT {ln(V/2V2)-x1 ln (1V1/2V2)}

B coefficient values are calculated using Jones-Dole equation. r =1+A c + B

(5)

The values of A & B are determined (TABLE 6) from the intercept & slope of the lines of plots of (/o -1) verses c. We observed positive values for all the systems. The B coefficient for APN in absence of additives is less and in presence of non-electrolyte sucrose is more. This increases with increase in percentage of alcohol which indicates the structural increases of solution from water to alcohol. The B coefficient of APN solution reflects the net structural effects of polar groups and hydrophobic benzene ring. REFERENCES

(4)

where,  , 1 & 2 are the viscosities of liquid mixtures, components (1) & (2) respectively, V1 & V2 are the molar volumes of components (1) & (2) respectively, x1 is the mole fraction of first component, R is the gas constant & T is the absolute temperature. The values are positive and changes parabolically with percentage of ethanol (Figure 2). The maximum Gibbs free energy of viscous flow for ethanol-water is 75.4598 KJ mole-1. The trend in maxima shows that G*E for NaCl is less than G*E for sucrose. This excess free energy increases with increase in concentration of APN keeping concentration of additive const. The values of G*E is much higher when APN and additives are present together. The positive values of G*E represent the size effect of mixing components. It is considered that if G*E is positive there are specific interactions like hydrogen bonding which exists between molecules of mixture[11].

[1] R.Gopal, M.A.Siddiqui, K.Singh; J.Indian Chem.Soc., 47, 504 (1970). [2] R.L.Bokhra, P.C.Verma; J.Indian Chem.Soc., 54, 1129 (1977). [3] R.Gopal, D.K.Agarwal, Rajendra Kumar; J.Phy.Chem., 84, 141 (1974). [4] R.L.Bokhra, M.L.Parmar; Aust.J.Chem., 27, 1407 (1974). [5] K.D.Treepathi; ‘Essentials of Medical Pharmacology’, 4th Ed., Jaypee Brothers Medical Pub (P) Ltd, New Delhi, (1999). [6] V.K.Sayal, S.Chavan, P.Sharma; J.Indian Chem.Soc; 82, 602-607 (2005). [7] J.D.Lee; ELCH, Publication London 4th Edition, (1991). [8] A.Pal, H.Kumar; Ind.J.Chem., 40A, 598 (2001). [9] R.J.Bearman, P.F.Jones; J.Chem.Phy., 33, 1432 (1960).